Design of high-specificity binders for peptide–MHC-I complexes.

Amino acid residues; Green fluorescent protein; Generative artificial intelligence; Cell surface antigens; HLA histocompatibility antigens; Protein-protein interactions; T cell receptors; Protein-ligand interactions; Deep learning

The article focuses on the design and development of proteins that specifically bind to peptide–MHC-I (pMHCI) complexes, which are crucial for immune surveillance and therapeutic applications. Using a computational approach called RFdiffusion, researchers created high-affinity binders for 11 different pMHC targets, demonstrating the ability to distinguish between target and off-target peptides. The designed proteins were incorporated into chimeric antigen receptors (CARs), leading to specific T cell activation against various disease-associated peptides, including those from viral and tumor-associated antigens. This method shows promise for generating targeted therapies that can effectively engage the immune system against a wide range of diseases. [Extracted from the article]

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